Inclusion Criteria- Children ages 1 to 18 years of age with sickle cell anemia confirmed by hemoglobin electrophoresis evaluation or HPLC;
- Informed consent from a parent or legal guardian and assent of participants;
- Children with history of stroke with event up to and within 30 days prior to signing the informed consent;
- Acceptance of HU therapy for at least two years.
Exclusion Criteria- Children with history of stroke with event occurring more than 30 days prior to signing the informed consent;
- Confirmed pregnancy or considering family planning - due to possible hydroxyurea-induced congenital anomalies or abnormal fetal growth. Adolescents who have started their menses must have a pregnancy test done every month prior to getting a prescription for HU;
- Children who are already on blood transfusion or HU therapy;
- Other exclusions: significant cytopenias [absolute neutrophil count (ANC) <1500/ul, platelets <150,000/ul, reticulocytes <80,000/ul, unless Hb is > 9 g/dl], renal insufficiency (creatinine > 0.8 mg/dl); other significant organ system dysfunction, or other contraindication to HU therapy; and history of seizures or diagnosis of epilepsy;
- Other significant organ system dysfunction based on the site investigators discretion;
- Any other condition, such as malnutrition, or chronic illness, which in the opinion of the site's Principal Investigator makes study therapy not advisable or unsafe;
- Active infections: bacterial, viral or fungal (tuberculosis, malaria, active hepatitis, osteomyelitis);
- Active chronic leg ulcers.